Molecular Data and the IPSS-R: How Mutational Burden Can Affect Prognostication in MDS

Abstract

Purpose of Review

The purpose of this study is to review established prognostic models in myelodysplastic syndromes (MDS) and describe how molecular data can be used to improve patient risk stratification.

Recent Findings

Somatic mutations are common in MDS and are associated with disease features including outcomes. Several recurrently mutated genes have prognostic significance independent of risk stratification tools used in practice. However, this prognostic impact can depend on the clinicogenetic context in which mutations occur. Qualitatively, SF3B1 mutations appear favorable only in patients with < 5% bone marrow blasts while mutations of several genes, including ASXL1, SRSF2, U2AF1, NRAS, and IDH2, appear adverse in this context. Mutations of TP53, RUNX1, and EZH2 appear adverse regardless of blast percentage. Consensus on how to best incorporate mutations into risk assessment is still being developed.

Summary

Somatic mutations can refine risk stratification and improve the accuracy of existing prognostic models, often upstaging or downstaging patients across the boundary of higher- and lower-risk MDS.

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A novel mutation in the COL2A1 gene in a patient with Stickler syndrome type 1: a case report and review of the literature

Stickler syndrome is a group of collagenopathies characterized by ophthalmic, skeletal, and orofacial abnormalities, with the degree of symptoms varying among patients. Mutations in the COL2A1, COL11A1, and COL11...

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Impact of therapy on genomics and transcriptomics in high-risk prostate cancer treated with neoadjuvant docetaxel and androgen deprivation therapy

Background: The combination of docetaxel chemotherapy and androgen deprivation therapy (ADT) has become a standard treatment for patients with metastatic prostate cancer. The recently accrued Phase III CALGB 90203 trial was designed to investigate the clinical effectiveness of this treatment approach earlier in the disease. Specimens from this trial offer a unique opportunity to interrogate the acute molecular response to docetaxel and ADT and identify predictive biomarkers. Methods: We evaluated baseline clinical data, needle biopsies and radical prostatectomy (RP) specimens from 52 (of 788) patients enrolled on CALGB 90203 at one high volume center. Pathology review, tumor and germline targeted DNA sequencing (n=72 genes), and expression profiling using Nanostring platform (n=163 genes) were performed to explore changes in critical prostate cancer pathways linked to aggression and resistance. Results: 3/52 patients had only microfocal residual cancer at prostatectomy. The most common alterations included TMPRSS2-ERG fusion (n=32), TP53 mutation or deletion (n=11), PTEN deletion (n=6), FOXA1 (n=6), SPOP (n=4) mutation, with no significant enrichment in post-treated specimens. We did not observe AR amplification or mutations. The degree of AR signaling suppression varied among treated tumors and there was up-regulation of both AR and AR-V7 expression as well as a subset of neuroendocrine and plasticity genes. Conclusions: These data support the feasibility of targeted and temporal genomic and transcriptome profiling of neoadjuvant-treated prostate cancer with limited formalin-fixed paraffin embedded tissue requirement. Characterization of the heterogeneity of treatment response and molecular outliers that arise post-treatment provides new insight into potential early markers of resistance.

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Microvascular reactivity monitored with near-infrared spectroscopy is impaired after induction of anaesthesia in cardiac surgery patients: An observational study.

BACKGROUND: Induction of anaesthesia causes significant macrohaemodynamic changes, but little is known about its effects on the microcirculation. However, alterations in microvascular perfusion are known to be associated with impaired tissue oxygenation and organ dysfunction. Microvascular reactivity can be assessed with vascular occlusion testing, which evaluates the response of tissue oxygen saturation to transient ischaemia and reperfusion. OBJECTIVE: The aim of the current study was to evaluate the effects of an opioid-based anaesthesia induction on microvascular reactivity. We hypothesised that despite minimal blood pressure changes, microvascular function would be impaired. DESIGN: Prospective, observational study. SETTING: Single-centre, tertiary university teaching hospital, Belgium. PATIENTS: Thirty-five adult patients scheduled for elective coronary artery bypass grafting surgery. INTERVENTION: Microvascular reactivity was assessed before and 30 min after anaesthesia induction by means of vascular occlusion testing and near-infrared spectroscopy. MAIN OUTCOME MEASURES: Tissue oxygen saturations, desaturation rate, recovery time (time from release of cuff to the maximum value) and rate of recovery were determined. RESULTS: Data are expressed as median (minimum to maximum). Tissue oxygen saturation was higher after induction of anaesthesia [70 (54 to 78) vs. 73 (55 to 94)%, P = 0.015]. Oxygen consumption decreased after induction, appreciable by the higher minimum tissue oxygen saturation [45 (29 to 69) vs. 53 (28 to 81)%, P

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Research ethics committee approval as reported for abstracts submitted to the annual Euroanaesthesia meeting.

BACKGROUND: The annual congress of the European Society of Anaesthesiology (ESA) is one of the largest anaesthesia congresses in the world and exhibits more than 1200 abstracts annually. OBJECTIVES: The aims of this study were to quantify the frequency of inadequate evidence of ethical approval for abstracts submitted to the ESA congress and to examine whether abstracts without appropriate ethical approval were subsequently accepted. DESIGN AND SETTING: All abstracts submitted in 2015 were adjudicated according to European ethical criteria. MAIN OUTCOME MEASURE: The proportion of submitted abstracts that lacked evidence of appropriate ethics committee approval. Secondary outcomes included the proportion of accepted abstract that lacked evidence of appropriate ethical approval; the proportion of correctly identified case reports; the proportion of accepted abstracts that lacked evidence of appropriate ethics committee approvals corresponding to location (within/outside Europe); and the proportion of accepted abstracts that lacked evidence of appropriate ethics committee approvals corresponding to a specific area of research. RESULTS: In total, 1792 abstracts were reviewed and 1572 (87.7%) involved humans. In 527 (29.4%), the authors failed to demonstrate adequate ethical approval with higher rates in abstracts submitted from Europe (32.1%) than the rest of the world (23.5%), P

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Calendar

Publication date: September 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 9





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Preoperative biliary drainage in hilar cholangiocarcinoma: Systematic review and meta-analysis

Publication date: September 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 9
Author(s): A. Celotti, L. Solaini, G. Montori, F. Coccolini, D. Tognali, G. Baiocchi
BackgroundThe role of preoperative biliary drainage (PBD) for hilar cholangiocarcinoma (HCC) remains unclear. The aim of this meta-analysis is to investigate the role of PBD in the treatment of potentially resectable HCC.MethodsAll studies reporting outcomes on patients with PBD vs without PBD were included. A systematic literature search was performed in PubMed, Embase, and the Cochrane Library for studies published between 1980 and 2016.ResultsInitial search identified 667 articles. Only 9 studies met the inclusion criteria and were included in this analysis. No significant differences in mortality were observed between the two groups (RR = 0,935; 95% CI = 0,612 to 1429; p = 0,463). Overall morbidity was significantly higher in PBD group (RR = 1266; 95% CI = 1039 to 1543; p = 0,011). No significant differences in transfusion rate, hospital stay, anastomotic leaks, abdominal collections and operative time, were found. Wound infections were significantly higher in PBD group.ConclusionsPBD seems to be associated with higher postoperative morbidity and increases the risk of wound infections. Further prospective studies are needed to better define the impact of PBD in outcomes after surgery for hilar cholangiocarcinoma.



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